Generation and cyclization of thiocarbonyl S‐ylides by reaction of diazocompounds with C‐sulfonyldithioformates

The unexpected 1,3‐benzodithiine derivatives 5b,c were obtained from the reactions of trimethylsilyldiazomethane 2 with C‐sulfonyldithioformates, bearing pentachlorophenylthio group, 1b,c via unprecedented cyclization of the transient thiocarbonyl ylides 4b,c . While the corresponding reaction with C‐sulfonyldithioformates, bearing phenylthio group, afforded 5a via [2 + 3]‐cycloadditive dimerization of a transient thiocarbonyl ylides 4a . Under the same reaction condition, C‐sulfonyldithioformates 1d–f react with diazomethane and/or phenyldiazomethane to afford the unsymmetrical 1,3‐dithiolane 7d,e and thiirane 8e,f derivatives, respectively. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:28–33, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20246     

Reactions with 3,6‐diaminothieno[2,3‐b]‐pyridines: Synthesis and characterization of several new fused pyridine heterocycles

6‐Aminopyridine‐2(1H)thiones 1 reacting with α‐halo‐compounds 2a–c afforded the alkylthiopyridine derivatives 3a–c which in turn cyclized to the corresponding thieno[2,3‐b]pyridine derivatives 4a–c . Several thieno[2,3‐b]pyridine derivatives 7, 16, 19 , pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine derivatives 6a,b, 11a–c, 21 and pyrido[3′,2′:4,5]thieno[3,2‐c]pyridazine derivatives 13, 17 were prepared starting from compounds 4a–c . © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:405–413, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20313     

Synthesis,Structural Characterization,and Biological Evaluation of Novel Substituted 1,3‐Thiazole Derivatives Containing Schiff Bases

In this study, thiazole derivatives containing Schiff bases ( 7a , 7b , 7c , 7d , 7e , 7f , 8a , 8b , 8c , 8d , 8e , 8f , 9a , 9b , 9c , 9d , 9e , 9f ) were synthesized in moderate to high yields (49–94%) using the Hantzsch reaction with thiosemicarbazone derivatives ( 5a , 5b , 5c ) and 2‐bromo‐1‐phenylethanone derivatives ( 6a , 6b , 6c , 6d , 6e , 6f ). The structures of synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR, elemental analyses, mass spectroscopy and X‐ray diffraction analysis techniques. Moreover, the synthesized compounds were tested for their in vitro antifungal activity and most of them exhibited moderate to good activity against Fusariumoxysporumf.sp. lycopersici.      

Kinetic studies on the reactions of 3‐isothiazolones with 2‐methyl‐2‐propanethiol

The kinetics of the ring‐opening reactions of the 3‐isothiazolones ( 1a–d ) with aqueous 2‐methyl‐2‐propanethiol has been explored at pH 4. The results strongly suggest that the reaction is second order in thiol and third order overall. Extrapolation of the kinetic data gives third‐order rate constants that lie in the order ( 1a ) > ( 1b ) > ( 1c ) > ( 1d ) in line with the known biological activity of these derivatives. The mechanism of the reaction is thought to involve attack by one thiol at the sulfur atom of the isothiazolone with the concomitant hydrogen bonding of a second thiol to the amide nitrogen. Calculations of the structure and electronic properties of the isothiazolones at the RHF 6‐31G** level are supportive. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 254–260, 2005     

Study of the oxidation of some catechols in the presence of 4‐amino‐3‐thio‐1,2,4‐triazole by digital simulation of cyclic voltammograms

Electrochemical oxidation of catechol and its derivatives ( 1a–d ) has been studied in the presence of 4‐amino‐3‐thio‐1,2,4‐triazole ( 3 ) at various pHs. Some electrochemical techniques such as cyclic voltammetry using the diagnostic criteria derived by Nicholson and Shain for various electrode mechanisms and controlled‐potential coulometry were used. Results indicate the participation of catechols ( 1a–d ) with 3 in an intramolecular cyclization reaction to form the corresponding 1,2,4‐triazino[5,4‐b]‐1,3,4‐thiadiazine derivatives. In various scan rates, based on an electron transfer–chemical reaction–electron transfer–chemical reaction mechanism, the observed homogeneous rate constants (k_obs) for Michael addition reaction were estimated by comparing the experimental cyclic voltammetric responses with the digital simulated results. The oxidation reaction mechanism of catechols ( 1a–d ) in the presence of 4‐amino‐3‐thio‐1,2,4‐triazole ( 3 ) was also studied. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 340–345, 2007     

Synthesis and antimicrobial activity of new functionalized derivatives of [1,2,4]triazolo[4,3‐a]pyrimidin‐5(1H)‐one

New functionalized 1,7‐diaryl‐6‐cyano‐1,2,4‐triazolo[4,3‐a]pyrimidin‐5(1H)‐one derivatives ( 5a–j ) were synthesized via reaction of 5‐cyano‐6‐phenyl‐2‐thiouracil 1 with the respective hydrazonoyl halides 2a–j and their biological activity was evaluated. The mechanism and the regioselectivity of the studied reactions are discussed. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:393–398, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20311     

Synthesis and interconversion of isomeric pyrrolotriazolopyrimidines

4‐Hydrazino‐7H‐pyrrolo[2,3‐d]pyrimidines 4 were cyclocondensed with formic acid or triethyl orthoformate to give 7H‐pyrrolo[3,2‐e][1,2,4]triazolo[1,5‐c]pyrimidines 6 and 7H‐pyrrolo[3,2‐e][1,2,4]triazolo[4,3‐c]pyrimidines 7 , respectively. The [4,3‐c] isomers 7 were rearranged into thermodynamically more stable [1,5‐c] isomers 6 . The identical compounds 6 were prepared using another route by reacting 3‐amino‐4‐imino‐7H‐pyrrolo[2,3‐d]pyrimidines 3 with formic acid or triethyl orthoformate. The reaction of 2‐amino‐3‐cyanopyrroles 1 with triethyl orthoformate gave N‐ethoxymethylene‐2‐amino‐3‐cyanopyrroles 2 . Further reaction with an equivalent of hydrazine hydrate provided 3‐amino‐4‐imino‐7H‐pyrrolo[2,3‐d]pyrimidines 3 , whereas treatment with excess of hydrazine hydrate, 3 rearranged to 4‐hydrazino‐7H‐pyrrolo[2,3‐d]pyrimidines 4 . Compounds 4 were also obtained by the treatment of N‐ethoxymethylene‐2‐amino‐3‐cyanopyrroles 2 in excess of hydrazine hydrate. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:265–273, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20295     

Synthesis of New Gluco‐, Galacto‐, and Mannopyranosylthiazoles,Thiazolidinones, and Pyranosylthiazlidin‐4‐ones from Sugar Thiosemicarbazone Derivatives

A new series of potentially biological active derivatives, namely alkyl‐2‐((4‐oxo‐2‐(phenylimino)‐3‐(β‐d ‐pyranosyl‐2‐ylamino)thiazolidine‐5‐ylidene)acetate ( 5a–f ), 4‐(4‐bromophenyl)thiazol‐2(3H)‐ylidene)hydrazinyl)‐β‐d ‐pyranosyl ( 4a–c ), and 5‐(4‐bromophenyl)‐2‐(phenylimino)‐3‐(β‐d ‐pyranosyl‐2‐ylamino)thiazolidine‐4‐one ( 6 ) were synthesized via a reaction of the sugar thiosemicarbazone derivatives with 2,4′‐dibromoacetophenone, dialkylacetylenedicarboxylate, and ethylbromoacetate, respectively. The structures of the synthesized compounds were established by spectroscopic methods (FT‐IR, ¹H NMR, ¹³C NMR, and 2D NMR) and elemental analyses. Furthermore, the effect of various solvents at reflux and also ambient temperature on the reactions of the sugar thiosemicarbazone with 2,4′dibromoacetophenone, diethyl acetylenedicarboxylate, and dimethyl acetylenedicarboxylate was investigated. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:200–207, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21083     

Synthesis of 1‐methyl‐, 4‐nitro‐, 4‐amino‐and 4‐iodo‐1,2‐dihydro‐3H‐pyrazol‐3‐ones

4‐Aminopyrazole‐3‐ones 4b, e, f were prepared from pyrazole‐3‐ones 1b‐d in a four‐step reaction sequence. Reaction of the latter with methyl p‐toluenesulfonate gave 1‐methylpyrazol‐3‐ones 2b‐d . Compounds 2b‐d were treated with aqueous nitric acid to give 4‐nitropyrazol‐3‐ones 3b‐d. Reduction of compounds 3b‐d by catalytic hydrogenation with Pd‐C afforded the 4‐amino compounds 4b, e, f. Using similar reaction conditions, nitropyrazole‐3‐ones derivatives 2c, d were reduced into aminopyrazole‐3‐ones 5e, f. 4‐Iodopyrazole‐3‐ones 7a, 7c and 8 were prepared from the corresponding pyrazol‐3‐ones 2a, 2c and 6 and iodine monochloride or sodium azide and iodine monochloride.     

Synthesis of Novel Benzofuran‐Gathered C‐2,4,6‐substituted Pyrimidine Derivatives Conjugated by Sulfonyl Chlorides: Orally Bioavailable,Selective, Effective Antioxidants and Antimicrobials Drug Candidates

In the present study, we have made an effort to develop the novel synthetic antioxidants and antimicrobials with improved potency. The novel benzofuran‐gathered C‐2,4,6‐substituted pyrimidine derivatives 5a , 5b , 5c , 5d , 5e , 5f , 6a , 6b , 6c , 6d , 6e , 6f , 7a , 7b , 7c , 7d , 7e , 7f , 8a , 8b , 8c , 8d , 8e , 8f , 9a , 9b , 9c , 9d , 9e , 9f were synthesized by simple and efficient four‐step reaction pathway. Initially, o‐alkyl derivative of salicylaldehyde readily furnish corresponding 2‐acetyl benzofuran 2 in good yield, upon the treatment with potassium tertiary butoxide in the presence of molecular sieves. Further, Claisen–Schmidt condensation with aromatic aldehydes via treatment with thiourea followed by coupling reaction with different sulfonyl chlorides afforded target compounds. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis and further screened for their antioxidant and antimicrobial activities. The results showed that the synthesized compounds 8b , 8e , 9b , and 9e produced significant antioxidant activity with 50% inhibitory concentration higher than that of reference, whereas compounds 7d and 7c produced dominant antimicrobial activity at concentrations 1.0 and 0.5 mg/mL compared with standard Gentamicin and Nystatin, respectively.     

Reactivity of 3‐(benzothiazol‐2‐yl)‐3‐oxopropanenitrile: A facile synthesis of novel polysubstituted thiophenes

The reaction of 3‐(benzothiazol‐2‐yl)‐3‐oxopropanenitrile 1 with active methylene reagents 2a–d and sulfur afforded polysubstituted thiophenes 3a–c . The synthetic potential of the β‐enaminonitrile moiety in 3a was explored. The reaction of 3a with active methylene reagents 2a–e afforded thieno[2,3‐b]pyridine derivatives 6–8. Refluxing of 3a with acetic anhydride alone, with acetic anhydride/pyridine mixture, or with carbon disulfide in pyridine afforded the acetamido 9, thieno[2,3‐d]pyrimidine 10, and pyrimidinedithiol 11 derivatives, respectively. The pyrimidinedithiol 11 was alkylated smoothly with methyl iodide to give the bis(methylthio) derivative 12. Also, compound 3a reacted with trichloroacetonitrile to give the thieno[2,3‐d]pyrimidine derivative 14. Compound 3a reacted with triethyl orthoformate or formamide to give the ethoxymethylideneamino 15 and thieno[2,3‐d]pyridine 16, respectively. Compound 15 reacted with hydrazine to afford thieno[2,3‐d]pyridine 17, which reacted with various reagents such as chloroacetyl chloride, ethyl cyanoacetate, diethyl oxalate, or chloroethylformate to give 1,2,4‐triazolo[1,5:1,6]pyrimidino‐[4,5‐b]thiophene derivatives 18a–c and 19, respectively. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:94–101, 2000     

Synthesis and Reactivity of Phenylthiourea Derivatives: An Efficient Synthesis of New Thiazole‐Based Heterocycles

Reaction of 1‐(5‐acetyl‐4‐methylthiazol–2‐yl)–3‐phenylthiourea 2 with hydrazonoyl chlorides ( 3a , 3b , 3c , 3d , 3e , 3f ) and 9 yielded the corresponding (thiazolyl)imino–1,3,4‐thiadiazole derivatives ( 6a , 6b , 6c , 6d , 6e , 6f ) and 12 , respectively. Reaction of 2 with ethyl chloroacetate 13 gave (thiazolyl)imino‐1,3‐thiazolidin‐4‐one derivative 15 , which upon condensation with aromatic aldehyde derivatives yielded the 5‐benzylidene derivatives ( 16a , 16b ). In addition, treatment of 2 with 3‐chloropenta‐2,4‐dione 17 afforded the corresponding (thiazolyl)imino‐1,3‐thiazole derivative 19 . The newly synthesized compounds were confirmed from their elemental analyses and spectral data.     

Synthesis of Bis(imidazole‐2‐thion‐4‐yl)phosphanes

Novel bis(imidazole‐2‐thion‐4‐yl)‐ phosphanes ( 2a–d ) were synthesized via lithiation of the precursor imidazole‐2‐thiones followed by the phosphanylation reaction. Oxidation of bis(imidazole‐2‐thion‐4‐yl)phosphane 2b–d with elemental sulfur and selenium led selectively and in good yields to the P‐thio ( 3b–d ) and P‐seleno ( 4c ) derivatives of bis(imidazole‐2‐thion‐4‐yl)phosphanes, respectively. The treatment of 2a,c with phosphorus trichloride gives the corresponding P‐chloro derivatives 5a,c . These compounds were unambiguously characterized by elemental analyses, spectroscopic and spectrometric methods, in addition by single‐crystal X‐ray structure analysis in the case of 2d . © 2012 Wiley Periodicals, Inc. Heteroatom Chem 00:1–7, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21043     

An efficient electrochemical method for synthesis of (1h‐1,2,4‐triazol‐3‐ylthio)benzen‐1,2‐diol derivatives

Electrochemical oxidation of catechols ( 1a–c ) has been studied in the presence of 3‐mercapto‐1,2,4‐triazole ( 3 ) as a nucleophile in water/acetonitrile (90/10) solutions. The results revealed that the quinones derived from catechols ( 1a–c ) participate in the Michael addition reactions with anion of 3‐mercapto‐1,2,4‐triazole ( 3 ) and are converted to the corresponding (1H‐1,2,4‐triazol‐3‐ylthio)benzen‐1,2‐diol derivatives ( 4a–c ). © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:644–649, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20359     

Synthesis and isomerization of thienotriazolopyrimidine and thienotetrazolopyrimidine derivatives with potential anti‐inflammatory activity

Several derivatives containing the thieno[2,3‐d]pyrimidine system were prepared starting from 2‐amino‐4,5‐dihydronaphtho[2,1‐b]thiophene‐1‐carbonitrile ( 1 ). In particular, the synthesis and structure characterization of 8,9‐dihydronaphtho‐ [1′,2′:4,5]thieno[3,2‐e][1,2,4]triazolo[4,3‐c]pyrimidine derivatives 13–16 and their isomerization to 8,9‐dihydronaphtho[1′,2′:4,5]thieno[3,2‐e][1,2,4]‐triazolo[1,5‐c]pyrimidine derivatives 17–20 under different suitable reaction conditions were reported and verified with X‐ray analysis. Moreover, compounds 13, 14 and 22 were tested as potential anti‐inflammatory agents and derivative 14 showed potent activity in carrageenan test. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:226–234, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20114     

Synthese neuer N-Vinylpyrrole

Syntheses of New N-Vinylpyrroles The reactions of pyrrolyl potassium ( 1 ) with (ethoxymethylene)malonic acid derivatives 2a–e yielded the carbanions 3a–e , which could be hydrolyzed to 4a–e , but with the exception of 4b they were not isolated, because a transformation to the N-vinylpyrroles 5a , c–e by elimination of ethanol took place; 1 reacted with 2b at 80°C to give 4b and 6 . Hydrolysis of 4b with KOH yielded 4g , which eliminated 1 mol of ethanol to form 5f , decarboxylation of which led to N-vinylpyrrole 7 . By cyclization of 5e under various conditions the pyrrolizines 8a , b are obtained, the hydrolysis of which did not give ketone 9 but only amino alcohol 10 . Some other cyclizations of 11a–c and 13 yielded the 3H-pyrrolizine derivatives 12a–c and 14 , respectively.     

Synthesis,characterization and catalytic properties of novel palladium(II) complexes containing aromatic sulfonamides: effective catalysts for the oxidation of benzyl alcohol

In this article, N‐(2‐aminophenyl)arylsulfonamides (1–5) were successfully synthesized by the reaction of o‐phenylenediamine and various benzenesulfonyl chlorides. The Schiff base derivatives (1a–f; 4e) of those compounds were obtained using different aldehydes. Then, a series of neutral‐four coordinate Pd(II) complexes (6–10) were prepared from the reaction of Pd(OAc)₂ and 1–5. On the other hand, when we tried to synthesize Pd(II) complexes containing Schiff base/sulfonamide ligands, two different situations were observed. Generally, when an electron‐donating group was attached to the imine fragment (1a–d) except for 1f, the Schiff base hydrolyzed and 6 was isolated. When an electron‐withdrawing group was attached to the imine fragment (1e, 4e), neutral four‐coordinate Pd(II) complexes (11–13) bearing Schiff base/sulfonamide ligands were isolated. The synthesized compounds were characterized by FT‐IR, elemental analysis and NMR spectroscopy. The complexes were used as a catalyst in the oxidation reaction of benzyl alcohol to benzaldehyde in the presence of H₅IO₆ in acetonitrile. All complexes showed satisfactory catalytic activity. The highest catalytic activity was obtained with 9. Copyright © 2012 John Wiley & Sons, Ltd.     

Radical Cyclization Reactions via Manganese(III) Acetate Leading to 2‐Thienyl‐Substituted Dihydrofuran Compounds

The 2‐thienyl‐substituted 4,5‐dihydrofuran derivatives 3 – 8 were obtained by the radical cyclization reaction of 1,3‐dicarbonyl compounds 1a – 1f with 2‐thienyl‐substituted conjugated alkenes 2a – 2e by using [Mn(OAc)₃] (Tables 1–5). In this study, reactions of 1,3‐dicarbonyl compounds 1a – 1e with alkenes 2a – 2c gave 4,5‐dihydrofuran derivatives 3 – 5 in high yields (Tables 1–3). Also the cyclic alkenes 2d and 2e gave the dihydrobenzofuran compounds, i.e., 6 and 7 in good yields (Table 4). Interestingly, the reaction of benzoylacetone (=1‐phenylbutane‐1,3‐dione; 1f ) with some alkenes gave two products due to generation of two stable carbocation intermediates (Table 5).     

A New and Facile Synthesis of Novel Pyrazolothienopyrimidines and Imidazopyrazolothienopyrimidines

4‐Amino‐3‐methyl‐1‐phenyl‐1H‐thieno[2,3‐c]pyrazole‐5‐carboxamide ( 5 ), which was synthesized by an innovative method, was used as a versatile precursor for synthesizing pyrazolothienopyrimidines and imidazopyrazolothienopyrimidines compounds. Reaction of amino thienopyrazole carboxamide 5 with triethyl orthoformate afforded thienopyrazolopyrimidine 6 . Chlorination of the latter compound, using phosphorus oxychloride afforded the chloro pyrazolothienopyrimidine 7 , which underwent nucleophilic substitution reactions with various primary and secondary amines to give the alkyl (aryl) amino pyrimidine compounds 8a–d . On the other hand, the reaction of chloropyrimidine 7 with thiourea afforded the pyrimidine thione compound 9 , which was alkylated with α‐halogentaed compounds to afford the S‐alkylated derivatives 10a–c . Also, chloroacetylation of the amino carboxamide 5 using chloroacetyl chloride yielded the chloromethyl pyrazolothienopyrimidine 12 , which underwent nucleophilic substitu‐ tion reactions with various primary and secondary amines to afford the alkyl (aryl) aminomethyl compounds 13a–f . The latter Compounds underwent Mannich reaction to give imidazopyrimidothieno‐ pyrazoles 14a–c . The newly synthesized compounds and their derivatives were fully characterized by elemental and spectral analysis.     

Synthesis and Antimicrobial Activity of Some Novel Substituted Bis‐Pyridone,Pyrazole, and Thiazole Derivatives

A variety of novel bis‐heterocyclic derivatives were synthesized via the reaction of bis‐cyanoacetanilide derivative 3 with various aromatic aldehydes (1:2 molar ratio), to give the corresponding bis‐arylidene derivatives 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m . On the other hand, reacting compound 3 with substituted 2‐hydroxybenzaldehydes 6a , 6b , 6c afforded 2‐iminochromene‐3‐carboxamides 7a , 7b , 7c . The reaction of compound 5 with malononitrile afforded the novel bis‐pyridones 9a , 9b , 9c , 9f , 9g , 9h . The reaction of 5 with hydrazine derivatives afforded pyrazoles 11a , 11b , 11c , 11d , 11e , 11f , respectively. Compound 3 reacts with phenyl isothiocyanate in the presence of potassium hydroxide at room temperature followed by addition of some different halo‐carbonyl compounds to afford bis‐poly‐functionalized thiazole derivatives 13a , 13b , 13c . The bis‐enamine derivative 15 reacts also with hydrazine hydrate, guanidine, and hydroxylamine to give bis‐pyrazole 17 , pyrimidine 19 , and isoxazole 21 derivatives, respectively. Some of the newly synthesized compounds show moderate to high antimicrobial activity.